Malek Mohammadi Laboratory
Our group is interested in understanding the molecular mechanism underlying cardiac regenerative ability of neonatal mice with the future aim of developing therapeutic targets to expand the regenerative window, prevent cardiovascular disease or treat patients in the future
Dr. Mona Malek Mohammadi
Life & Brain Center
Venusberg-Campus 1
53127 Bonn
Research
Cardiovascular regeneration
Neonatal mice, akin to human neonates, demonstrate cardiac regeneration following injury and adaptation to pressure overload. However, this regenerative capacity diminishes shortly after birth. Our research group aims to delve into cellular and molecular mechanisms underlying cardiac regeneration, plasticity, and adaptive response of neonatal mouse heart under pressure overload. By uncovering these intricate mechanisms, we aspire to pave the way for the development of future therapeutic interventions for patients.
Our expertise lies in executing various surgical models tailored to explore cardiac regeneration, including cryoinjury, myocardial infarction, neonatal model of transverse aortic constriction (nTAC), and neonatal model of pulmonary artery banding (nPAB). These models induce ischemic injury or pressure overload in the left ventricle (LV) or the right ventricle (RV), respectively.
Images of heart sections 14 days post sham, nTAC or nPAB surgery at P1
Cardiomyocytes are stained against Troponin T and Ki67 is stained in green.To monitor structural, functional, and morphological changes throughout the heart, we employ state-of-the-art echocardiography techniques, encompassing 2D, 3D, and 4D imaging modalities. This enables comprehensive follow-up assessments, facilitating a deeper understanding of cardiac dynamics in response to various stimuli.
4D Echocardiography
4D Volume assessment of the heart
3D Echocardiographic imaging of the entire heart at postnatal day 21
The right ventricle is contoured in red and the left ventricle is contoured in turquoise.
To dissect the role of different cell types in the complex process of cardiac regeneration, we utilize cutting-edge strategies, including genetic fate mapping, enabling lineage tracing of specific cell subpopulations within the heart. This approach empowers us to investigate their roles and contribution to the overall adaptive response of the heart.
Genetic fate mapping of fibroblasts
A) Genetic structure of mTmG mouse model, which expresses EGFP upon Cre expression under a cell type specific promoter
B) Macroscopic images of the transgenic heart at postnatal day 14 in bright field (BF) and fluorescence channels showing Tomato, GFP expression in the heart
We employ single-cell and bulk RNA sequencing, along with in vitro cell culture experiments, to explore and elucidate the intricate cellular crosstalk with the aim of unraveling the potential involvement of cellular interactions in the process of cardiac regeneration.
Neonatal mouse cardiomyocytes and fibroblasts co-culture
Cardiomyocytes and fibroblasts are stained against Troponin T and PDGFRa, respectively. EDU staining in green was used to assess cell cycle activity
Leader of the lab
Dr. Mona Malek Mohammadi
PhD
Assistence
Research assistants / postdocs
PhD students
Alumni
Adrian Goldspink
BonFor awards young scientist
Dr. Malek Mohammadi received BONFOR research award at the Bonfor symposium, 2024.
GNPI awards three prizes to the UKB
Dr. Fabian Ebach received research award at the 50th German Society of Neonatology and Pediatric Intensive care (GNP), 2024.
Abstractprize of the Segnitz-Ackermann-Foundation
Julia Nicke received the Segnity-Ackermann-Stiftung award at the basic science meeting of German Society of Cardiology (DGK), 2023.
Dr. Malek Mohammadi received Young Investigator Award from International Society of heart Research (ISHR), 2023.
T. Hu*, M. Malek Mohammadi*, F. Ebach, M. Hesse, M. I. Kotlikoff, B.K. Fleischmann. Right ventricular cardiomyocyte expansion accompanies cardiac regeneration in newborn mice after large left ventricular infarcts. JCI insight 2024 Feb 6;9(5):e176281. *Contributed equally.
- M. Szaroszyk, B. Kattih, A. Martin-Garrido, F. A. Trogisch, G. M. Dittrich, A. Grund, A. Abouissa, K. Derlin, M. Meier, T. Holler, M. Korf-Klingebiel, K. Völker, T. G.Macedo, C. P. Tortola, M. Boschmann, N. Huang, N. Froese, C.Zwadlo, M. Malek Mohammadi, X. Luo, M. Wagner, J. Cordero, R. Geffers, S. Batkai, Th.Thum, N. Bork, V. O. Nikolaev, O. J. Müller, H. A. Katus, A. El-Armouche, Th. Kraft, J. Springer, G. Dobreva, K. C. Wollert, J. Fielitz, S. von Haehling, M. Kuhn, J. Bauersachs & J.Heineke. Skeletal muscle-derived Musclin protects the heart during pathological overload. Nature communication 2022. 149 (2022).
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M. Malek Mohammadi, A. Abouissa, & J. Heineke, A surgical mouse model of neonatal pressure overload by transverse aortic constriction. Nat Protoc (2020)
- M. Malek Mohammadi, A. Abouissa, A. Isyatul, Y. Xie, J. Cordero, A. Shirvani, A. Gigina, M. Engelhardt, F. Trogisch, R. Geffers, G. Dobreva, J. Bauersachs, J. Heineke. Induction of cardiomyocyte proliferation and angiogenesis protects neonatal mice from pressure overload-associated maladaptation. JCI insight 2019 23; 5. pii: 128336.
- A. Grund, M. Szaroszyk, M. Korf-Klingebiel, M. Malek Mohammadi, F.Trogisch, U. Schrameck, A. Gigina, Ch. Tiedje, M. Gaestel, Th. Kraft, J. Hegermann, S. Batkai, Th. Thum, A. Perrot, C. Remedios, E. Riechert, M. Völkers, Sh. Doroudgar, A. Jungmann, R. Bauer, X. Yin, M. Mayr, K. Wollert, A. Pich, H. Xiao, H. Katus, J. Bauersachs, O. Müller, J. Heineke. TIP30 counteracts cardiac hypertrophy and failure by inhibiting translational elongation. EMBO Mol Med (2019)11: e10018.
- Grund A, Szaroszyk M, Döppner JK, M. Malek Mohammadi, Kattih B, Korf-Klingebiel M, Gigina A, Scherr M, Kensah G, Jara-Avaca M, Gruh I, Martin U, Wollert KC, Gohla A, Katus HA, Müller OJ, Bauersachs J, Heineke J.A gene therapeutic approach to inhibit CIB1 ameliorates maladaptive remodeling in pressure overload. Cardiovasc Res. 2018 1; 115(1):71-82.
- M. Malek Mohammadi, Kattih B, Grund A, Froese N, Korf-Klingebiel M, Gigina A, Schrameck U, Rudat C, Liang Q, Kispert A, Wollert KC, Bauersachs J, Heineke J. The transcription factor GATA4 promotes myocardial regeneration in neonatal mice. EMBO Mol. Med. 2017; 9(2):265-279.
- Appari M, Breitbart A, Brandes F, Szaroszyk M, Froese N, Korf-Klingebiel M, M. Malek Mohammadi, Grund A, Scharf GM, Wang H, Zwadlo C, Fraccarollo D, Schrameck U, Nemer M, Wong GW, Katus HA, Wollert KC, Müller OJ, Bauersachs J, Heineke J. C1q-TNF-Related Protein-9 Promotes Cardiac Hypertrophy and Failure. Circ Res. 2017 6;120(1):66-77